As pharma looks for better ways to build its drug pipelines, researchers are improving upon existing technologies and broadening their usage. At CHI’s recent “High Content Analysis” conference, presenters discussed new and revamped tools, and showed how these advances are helping pharma companies keep their drug pipelines active and productive.
According to Louis Stancato, Ph.D., senior research advisor, cancer growth and translational genetics at Eli Lilly & Co., phenotypic drug discovery (PDD) was previously laborious, inefficient, and often led to dead ends. “But the advent of higher volume informatics technologies, together with the high content imaging (HCI) piece, really makes PDD possible in a way that wasn’t tenable until now.”
His presentation examined how HCI subpopulation analysis tools enable a high-resolution look into cancer cell function. “This discipline is ideally suited to HCI applications. By incorporating custom in-house informatics tools, we can advance molecules with novel mechanisms of action through the lead-generation process, in particular, chemical series previously discarded owing to perceived failure in conventional targeted approaches.”
Dr. Stancato says that informatics experts help his team design custom algorithms, custom analyses, and data viewers that help find phenotypic fingerprints of interest. “Iteratively, we run our SAR looking at this phenotypic fingerprint in much the same way a chemist would look at an IC50 against an enzyme.
“We might look at upwards of 10 different data points from the same cell, synthesized to give us a number that we can then use to assess our structure activity relationships. This past summer, we launched an externally focused phenotypic drug discovery effort, called PD2 which is an open, global collaboration with academic and biotech institutions to help discover molecules.”
Dr. Stancato also examined case studies of molecules that could not have been identified any other way. They were essentially thrown away because they did not work in the targeted setting the way they were originally intended. “And if it weren’t for the imaging approach, we never would have known.”
Dr. Stancato’s group has helped many researchers with their imaging and informatics approaches by phenotypically showing molecules that were thought to behave similarly, actually behaved differently when looked at using his group’s informatics tools. “Everything we do results in a phenotypic change regardless of where it is, and that response will define whether or not the molecules we identify will help patients.”